Various snake venom peptides have been extensively evaluated for use as antithrombotic agents. Recently, it was determined that the snake venom peptide sarafotoxin S6b (S6b) is structurally similar to the potent vasoactive hormone endothelin-1 (ET-1), which has been shown to inhibit agonist-induced platelet aggregation. The potential in vivo antithrombotic activity of S6b was compared with that of ET-1, a much more potent pressor agent than S6b, by evaluating the effects of S6b and ET-1 (0.5 microgram/kg i.v.) on repetitive platelet thrombus formation (RPTF) in the stenosed canine circumflex coronary artery. In this model platelets adhere to the damaged vessel wall near a mechanically produced stenosis. As platelets aggregate at this site, blood flow gradually declines until the vessel is completely occluded. The thrombus is then physically dislodged, thus restoring flow. The blood flow pattern resulting from RPTF is referred to as cyclic flow reductions (CFRs). Injection of S6b or ET-1 blocked RPTF, as indicated by inhibition of CFRs. On a rating system of 0 (no effect) to 3 (complete inhibition), S6b and ET-1 produced CFR ratings of 1.8 +/- 0.5 (n = 6) and 2.0 +/- 0.4 (n = 6), respectively. This effect was not blocked by pretreatment with aspirin at 5 mg/kg i.v., a dose that abolishes arachidonic acid-induced ex vivo platelet aggregation (CFR scores for S6b and ET-1 were 2.6 +/- 0.2, n = 5 and 2.0 +/- 0.3, n = 5, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)